The goal of this project is to develop improved drug therapies for nervous system disease. Clinical and preclinical investigations seek to elucidate how the activity of specific transmitter systems relate to neuropsychiatric function. Based on these relationships, novel pharmaceutical agents are evaluated for their ability to influence central synaptic processes and thus modify neurologic symptoms. Major topics now under study include: 1) evaluations of human transmitter system function in the brain generally (through assays of endogenous or radioactively labeled transmitters or their metabolites in spinal fluid) or locally (by means of positron emission tomography using the fluorodeoxyglucose method), and 2) preclinical and clinical tests of the ability of selected dopamine agonists, GABAmimetics, and neuropeptide analogs to influence motor and cognitive behavior.